The lateral geniculate nucleus (LGN) serves as the primary thalamic relay for the transfer of retinal information to visual cortex. Despite the traditional view that the LGN plays a passive role in this information transfer, there is increasing evidence that the LGN serves a dynamic role in this process. In addition to sensory signaling, thalamocortical circuits play a role in alterations of behavioral states (e.g., sleep/wake, attention, and arousal), and certain pathophysiological conditions such as certain generalized epilepsies. The gating properties of thalamic nuclei, including the LGN, result from the integration of the intrinsic properties of thalamic neurons, synaptic organization and activity of thalamic pathways, and impinging influence of neuromodulators. Our long-range goals are to understand these various processes, and ultimately gain insight into how visual information is processed at the thalamic level. An understanding of these processes in the "normal" state should provide insight to potential abnormalities that may give rise to pathological conditions. The proposed experiments will focus on the regulation of thalamocortical activity by a class of putative neuromodulators: neuropeptides. The thalamus receives a rich peptidergic innervation from brainstem, neocortical and thalamic neurons. These experiments involve a combined anatomical, physiological, and pharmacological approach to investigate the functional role of certain neuropeptides that are localized within thalamocortical circuits, including vasoactive intestinal peptide (VIP), substance P (SP), and cholecystokinin (CCK). Intracellular recordings using the whole cell configuration will be used to access the actions of these peptides on neurons in the LGN and thalamic reticular nucleus using an in vitro brain slice preparation. Extracellular recordings will be used to study the role of the peptides on thalamocortical circuit activity. The specific aims are designed to determine the cellular mechanisms by which these neuropeptides alter excitability of individual thalamic neurons and their subsequent influence on synaptic transmission. Our working hypothesis is that certain neuropeptides serve as endogenous neuromodulators that are released in an activity-dependent manner and produce long-lasting changes in neuronal excitability, thereby having a significant role in the gating of visual information through the LGN. Our findings will provide not only new insights on the functional role of neuropeptides, but also how gating properties of the LGN are influenced by long-lasting modulatory influences